Adopted: 21 November 2014
Date Filed: 03 February 2015

I. RATIONALE
On 13 October 2014, Administrative Order No. 2014-0034 was issued to (a) update and streamline regulatory approaches in licensing of drug establishments, (b) provide faster access of drug products to the public; and(c) promote transparency through the universal use of electronic transaction.

In line with the new rules and regulations on the licensing of establishments classified as drug manufacturers and its subclass (packer/repacker/trader), the Food and Drug Administration (FDA) hereby prescribes the requirements for application for initial and renewal issuance of License to Operate (LTO), variations, as well as other guidelines relevant to these establishments.

II. LICENSE TO OPERATE (LTO) APPLICATIONS

1. Documentary Requirements
   
   

   1)	Application Form
   	A completely filled-out and notarized application form signed by the pharmacist and owner/authorized representative must be submitted.
   2)	Proof of Business Name Registration
   	A valid proof of business name registration must be submitted:
   	(a)	For single proprietorship - Certificate of Business Registration issued by the Department of Trade and Industry (DTI)
   	(b)	For corporation, partnership and other juridical person - Certificate of Registration issued by the Securities and Exchange Commission (SEC) and Articles of Incorporation
   	(c)	For cooperative - Certificate of Registration issued by the Cooperative Development Authority and the approved by-laws
   	(d)	For government-owned or controlled corporation - the law highlighting the provision creating such establishment.
   	The proof of business name registration must specify the exact and complete address, e.g., unit number, floor, building, lot, block, phase, street, barangay, city/municipality, province, where applicable.
   3)	Credentials of the Pharmacist and Other Qualified Personnel
   	The credentials of the identified pharmacist-in-charge for a specific activity must be submitted, which include:
   	(a)	Valid PRC ID
   	(b)	Certificate of Attendance to appropriate FDA Licensing Seminar
   	(c)	Resignation letter of the pharmacist from previous employer (if previously employed).
   	The other qualified personnel shall be listed, which include the (1) production manager/head. (2) quality assurance manager/head, (3) quality control manager/head, (4) authorized person for batch release, and (5) pharmacovigilance officer. The credentials will not be submitted during application but may be verified during inspection.
   4)	Risk Management Plan
   	A general Risk Management Plan (RMP) for the establishment must be submitted. The RMP shall contain details on how to identify, characterize, prevent or minimize risk relating to the products they engage with. These shall include pharmacovigilance activities and interventions of the establishment to manage the risks.
   5)	Location Plan
   	A sketch of the location of the establishment must be submitted which shall be used for inspection purposes. This sketch must indicate clear directions with identified landmarks to locate the establishment.
   	In addition, the Global Positioning System (GPS) Coordinates in decimal degrees (DD) [Latitude and Longitude] must be indicated in the submission.
   6)	Site Master File
   	The Site Master File (SMF) must be submitted, in accordance with the latest edition of the Pharmaceutical Inspection Cooperation Scheme (PIC/s) - Good Manufacturing Practice (GMP).
   7)	Proof of Payment
   	Proof of payment (e.g., official receipt or authorized bank payment slip) must be included as proof of filing of application.
   8)	Self-Assessment Toolkit
   	To guide and facilitate the submission, a Self-Assessment Toolkit (SATK) must be submitted, which will also serve as the worksheet during evaluation of FDA.
   	The list of documentary requirements for initial and renewal applications of LTO, reissuance of lost or destroyed LTO, as well as voluntary cancellation is attached as Annex A[*] .

   
   
2. Evaluation of Application
   
   

   1)	Desktop Evaluation
   	All applications shall be initially reviewed by the respective FDA Regional Field Offices to determine compliance with the administrative and technical requirements.
   	The FDA, in the course of its evaluation may require additional or supplemental documents as proof of compliance to the existing regulations.
   2)	Pre-opening Inspection
   	After evaluation of the LTO application, the establishment shall be subjected to pre-opening inspection to determine compliance with the existing guidelines on Pharmaceutical Inspection Cooperation Scheme (PIC/S)-Good Manufacturing Practices (GMP).
   	In addition to the documentary requirements submitted during application (Section II, A of this Circular), the following documents shall be verified during inspection:
   	Quality Management System Quality Manual and Standard Operating Procedures Contract Agreement (e.g., Manufacturing/ Packing/ Repacking Agreement for Manufacturer-Trader, Packing for Manufacturer-Packer, Repacking for Manufacturer-Repacker) Qualification and Validation Documents Master and Batch Production Records Specifications Credentials of other qualified personnel Proof of Ownership/Lease Agreement of the space/bldg. by the establishment occupied Relevant reference materials (e.g., Republic Acts, PIC/s-GMP Guide, standard practice guidelines) Other procedures, protocols, records, and reports as required by PIC/s- GMP
   	The abovementioned additional documents will serve as proof of compliance by the establishment with the existing regulations on licensing.
   	A report shall be issued to the drug establishment after inspection, which shall be the basis for the further decision/action of FDA (e.g., approval/ disapproval of an application for LTO, and/or for such other purposes).

   
   
3. Post-licensing Inspection
   
   All drug manufacturers and its subclass with approved LTO shall be subjected to routine inspection following the applicable provisions mentioned for pre-opening inspections under Section II, B of this Circular. In addition, major variation applications may require post-licensing inspection prior to the approval of such variation. Drug manufacturers and its subclass which are subject to regulatory action due to different triggers (e.g., violation of any of the provisions of FDA laws, rules and regulations, and any other laws related thereto, occurrence of adverse drug reactions as well as other quality, safety, and/or efficacy issues) shall also be inspected.
   
   
4. Application for Variation
   
   The following are the applicable variations to an approved LTO as drug manufacturer and its subclass:
   
   

   1)	Major Variation
   	(a)	Change of Ownership
   	(b)	Additional Production Line (e.g., sterile, penicillin)
   	(c)	Transfer of Location
   	(d)	Change of Activity
   2)	Minor Variation - Prior Approval
   	(a)	Expansion of Establishment
   	(b)	Change of Business Name
   	(c)	Zonal Change in Address
   3)	Minor Variation -Notification
   	(a)	Change of the Pharmacist or other Qualified Personnel
   	(b)	Deletion of Activity
   	(c)	Transfer/Addition of Warehouse

   
   FDA should be duly informed of any changes to the approved LTO, whether or not these are classified as variations described above. Other changes may also be added to the variations mentioned, which shall be subject of an appropriate regulation.
   
   The list of documentary requirements for the abovementioned variations is attached as Annex B^[*] .
   
   All variations are subject to the existing variation/amendment fee, except for transfer of location which is subject to initial payment for two (2) years validity of LTO.
   
   Drug manufacturer and its subclass applying for minor variations may continue business operations provided that an application for such variation has already been filed.
   
   
5. Accessibility
   
   All electronic fillable forms shall be made accessible at the FDA Website.
   

III. EXEMPTION IN PROVIDING ANOTHER PHARMACIST FOR ADDITIONAL LICENSED ACTIVITY
Exemption may be granted to Drug Manufacturer-Repacker and Drug Manufacturer-Trader pharmacist to handle another non-manufacturing activity except retailing, provided that the following conditions are satisfied:

1)	The activities sought to be licensed belong to one establishment only; establishment herein shall refer to a single business entity with the same business name registration and ownership who may engage in more than one licensed business activity;
2)	The activities to be handled by the pharmacist are confined only in one office and warehouse within the same premises.

This exemption shall be duly noted in the application indicating the pharmacist ™s duties and responsibilities as well as the schedule and hours of supervision to each establishment signed both by the pharmacist-in-charge and the owner/authorized representative.

IV. RESPONSIBILITIES OF OTHER IMPLEMENTING OFFICES
Consistent with the regulatory powers provided under (3), c, Sec. 2, Article III, Book I of the implementing rules and regulations of Republic Act No. 9711, FDA and its Regional Field Offices through the Director General may call on the assistance of any department office and/or government agency for the effective implementation of its rules and regulations.

In addition, Local Government Units (LGUs) are enjoined in monitoring licensed drug manufacturers in their localities for their compliance to the existing laws and their respective rules and regulations. Any violation found by the LGU inconsistent with the FDA rules and regulations shall be reported to FDA for regulatory action.

V. TRANSITORY PROVISIONS
Existing licensed establishments are required to submit their Risk Management Plan and GPS Coordinates upon renewal of their LTO.

VI. REPEALING CLAUSE/SEPARABILITY CLAUSE
Provisions of previous FDA circulars and memoranda that are inconsistent with this issuance are hereby withdrawn, repealed, and/or revoked accordingly. In case any part, term or provision of this FDA Circular is declared contrary to law or unconstitutional, other provisions which are not affected remain in force and effect.

VII. EFFECTIVITY
This Circular shall take effect upon approval and signature by the FDA Director General.


(SGD) ATTY. NICOLAS B. LUTERO III, CESO III
Assistant Secretary of Health
OIC, Food and Drug Administration